This is an application for a supplement to a broadly based, interdisciplinary, program project on the physiological basis of pulmonary disease. The chief emphasis is on fundamental aspects of the functions of the lung including mechanisms of blood flow and ventilation, and the relationships between these and pulmonary gas exchange. An important feature of the program is an attempt to relate advances in non-medical departments in a number of areas to problems of pulmonary diease. The departments from which the project investigators come include: Medicine, Scripps Institution of Oceanography, Applied Mechanics and Engineering Sciences, and Mathematics. Project 6 in the Program Project is devoted to a method of determining virtually continuous distributions of ventilation-perfusion ratios in normal and diseased lungs. The method is based on the infusion of multiple inert gases and measurements of their steady-state concentration in arterial blood and expired gas. This method has given valuable additional information about the mechanism of impaired gas exchange in a number of diseased states. The present supplement aims to expand this method so that we can determine the distribution of lung volume, lung tissue plus water volume, ventilation and blood flow in normal and diseased lungs. The proposed new method consists of meassring the inert gas concentrations during unsteady state conditions of washin or washout. Because the number of gas analyses will be considerably increased over that in the steady-state approach, the practical use of this method requires that an alternate method of analysis of the inert gases be developed. We propose to use a special respiratory mass spectrometer. The new method will be tested in anesthetized dogs including normal animals and those with experimental pulmonary edema and embolis. Subsequently measurements will be made on patients with asthma, acute respiratory failure, and chronic obstructive lung disease. It is hoped that the method will considerably improve our ability to characterize structure-function relationships of abnormal gas exchange in lung disease in particular it might be useful in the early detection of increased lung water, and in elucidating the mechanism of instability of lung units with low ventilation-perfusion ratios.